A Study to Evaluate the Efficacy, Response Duration and Safety of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine Treatment (H1)

A Phase III, Multicenter, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study to Evaluate the Efficacy, Response Duration and Safety of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria Who Remain Symptomatic Despite Antihistamine Treatment (H1)

The study is a global Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab administered subcutaneously as an add-on therapy for the treatment of adolescent and adult patients aged 12-75 who have been diagnosed with refractory CIU and who remain symptomatic despite standard-dosed H1 antihistamine treatment.

The trial incorporated a Type I error control plan, as follows:

The testing of the primary endpoint was conducted in the following hierarchical order. A p-value that is less than 0.05 can only be claimed statistically significant if statistical significance has been claimed at the previous stage.

• Stage 1: Omalizumab 300-mg group vs. placebo
• Stage 2: Omalizumab 150-mg group vs. placebo
• Stage 3: Omalizumab 75-mg group vs. placebo

A hierarchical analysis of the secondary endpoints was performed for each dose found to be significant in the primary endpoint. A p-value that is less than 0.05 can only be claimed statistically significant if statistical significance has been claimed at the previous stage.

• Stage 1: Change from baseline in Urticaria Activity Score (UAS7) at Week 12
• Stage 2: Change from baseline in the weekly number of hives score at Week 12
• Stage 3: Time to weekly itch severity score Minimally Important Difference (MID) response at Week 12
• Stage 4: Proportion of patients with UAS7 ≤ 6 at Week 12
• Stage 5: Proportion of weekly itch severity score MID Responders at Week 12
• Stage 6: Change from baseline in weekly size of the largest hive score at Week 12
• Stage 7: Change from baseline in overall Dermatology Life Quality Index (DLQI) score at Week 12
• Stage 8: Proportion of angioedema-free days from Week 4 to Week 12

Inclusion Criteria:

• Diagnosis of Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) CIU/CSU refractory to H1 antihistamines at the time of randomization.

Exclusion Criteria:

• Treatment with an investigational agent within 30 days prior to screening.
• Weight < 20 kg (44 lbs).
• Clearly defined underlying etiology for chronic urticarias other than CIU.
• Evidence of parasitic infection.
• Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or other skin disease associated with itch.
• Previous treatment with omalizumab within a year prior to screening.
• Routine doses of the following medications within 30 days prior to screening: Systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide.
• Intravenous (IV) immunoglobulin G (IVIG), or plasmapheresis within 30 days prior to screening.
• Regular (daily/every other day) doxepin (oral) use within 6 weeks prior to screening.
• Any H2 antihistamine use within 7 days prior to screening.
• Any leukotriene receptor antagonist (LTRA) (montelukast or zafirlukast) within 7 days prior to screening.
• Any H1 antihistamines at greater than approved doses within 3 days prior to screening.
• Patients with current malignancy, history of malignancy, or currently under work-up for suspected malignancy except non-melanoma skin cancer that has been treated or excised and is considered resolved.
• Hypersensitivity to omalizumab or any component of the formulation.
• History of anaphylactic shock.
• Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients.
• Evidence of current drug or alcohol abuse.
• Nursing women or women of childbearing potential, unless they meet the following definition of post-menopausal: 12 months of natural amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 milli-international units per milliliter (mIU/mL) or 6 weeks post surgical bilateral oophorectomy (with or without hysterectomy) or hysterectomy or are using one or more of the following acceptable methods of contraception: surgical sterilization, hormonal contraception, and double-barrier methods.